The present invention relates to an adsorbent for adsorbing and removing endogenous cannabinoid from body fluid, a process for adsorbing and removing endogenous cannabinoid, and an adsorber for endogenous cannabinoid.
It is known that cannabinoids, the main substance of the physiological action of marijuana (cannabis), brings about mental effects such as hallucination and feeling of euphoria. As cannabinoid receptors, a receptor (CB1) expressed in central nerves and a receptor (CB2) expressed in peripheral immune cells are known. Endogenous ligands to these cannabinoid receptors, i.e., the ligand generated in living bodies are called endogenous cannabinoid. Known examples of the endogenous cannabinoid are anandamide and 2-arachidonoylglycerol (hereinafter referred to as 2-AG).
The endogenous cannabinoid bears various physiological activities such as (1) drop in blood pressure and bradycardia for cardiovascular system, (2) inhibition of NO generation in macrophages for immune system, (3) defect of memory and inhibition of pain sensation for central nerve system, and (4) induction of endothelial cell apoptosis for coagulation fibrinolysis system.
Recently, it became clear that anandamide is generated in macrophage and 2-AG is generated in blood platelet by means of lipopolysaccharide stimulus (hereinafter referred to as LPS). It is also observed that the generated endogenous cannabinoid causes drop in blood pressure. Furthermore, some raises possibility that the endogenous cannabinoid generated in macrophage or blood platelet is responsible for the blood pressure drop in septic shock. In fact, there is a report that concentrated endogenous cannabinoid was detected in the blood of patients with septic shock.
From these facts, a treatment is expected for the blood pressure drop in septic shock and the like by removing endogenous cannabinoid from body fluid of patients. However, no process for adsorbing and removing endogenous cannabinoid has been available so far. Hence, there has been considerable demand for such processes. Yin Wang et al reported that the adsorption of anandamide was possible by means of a substance obtained by fixing an antibiotic, polymyxin B (FEBS Letters, vol. 470, pp151-155, 2000). However, many steps are required in order to prepare such an adsorbent. Besides, the polymyxin B, one of the antibiotics, is very expensive. For these reasons, there is a desire for a process for adsorbing and removing endogenous cannabinoid by using a lower-price substance.
The present invention was carried out in order to solve the above problems. The object of the present invention is to provide an adsorbent which can adsorb and remove endogenous cannabinoid in body fluid efficiently, a process for adsorbing and removing endogenous cannabinoid in body fluid by using the adsorbent, and an adsorber for endogenous cannabinoid.
Intense studies were conducted as to an adsorbent which can adsorb and remove endogenous cannabinoid in body fluid efficiently. As a result, the present invention has been completed based on the findings that an adsorbent obtained by fixing a compound having a log P value of at least 3.50 on a water-insoluble carrier can adsorb and remove endogenous cannabinoid efficiently.
That is, the present invention relates to an adsorbent for endogenous cannabinoid obtained by fixing a compound having a log P value (P indicating distribution coefficient of octanol-water system) of at least 3.50 on a water-insoluble carrier.
The water-insoluble carrier is a water-insoluble porous carrier in a preferred embodiment.
The endogenous cannabinoid is anandamide in a preferred embodiment.
The endogenous cannabinoid is 2-AG in a preferred embodiment.
The present invention also relates to a process for adsorbing and removing endogenous cannabinoid comprising a step of contacting the adsorbent of endogenous cannabinoid with fluid containing endogenous cannabinoid.
The fluid is body fluid in a preferred embodiment.
The present invention also relates to an adsorber for endogenous cannabinoid comprising a container having an inlet and an outlet, and a means for preventing the adsorbent from escaping outside the container, wherein the container is filled with the adsorbent of endogenous cannabinoid.